Imidazol-5-one as an Acceptor in Donor–Acceptor Cyclopropanes: Cycloaddition with Aldehydes

Abstract

Spiro­[imidazol-5-one-4,1′-cyclopropanes] behave as donor–acceptor (D–A) cyclopropanes in a formal cycloaddition reaction with aldehydes. The activation of such type of cyclopropanes is achieved with an equivalent of Brønsted acid. The reaction proceeds in high yields of 51–92% and demonstrates moderate diastereoselectivity at the quaternary stereocenter, which is determined by the electron-donating nature of the aldehyde partner. The ease of separation of stereoisomers allowed the creation of a library of 44 spiroannulated tetrahydrofurans with various substitution patterns.

Recent Advances in Stereoselective Ring Expansion of Spirocyclopropanes: Access to the Spirocyclic Compounds

“…Most recently, Baranov and co-workers demonstrated the synthesis of spiro-annulated tetrahydrofuran derivatives 61 and 61′ by employing spirocyclopropyl imidazol-5-ones 60 and aldehydes in the presence of TsOH, wherein the spirocyclopropane unit is flanked by a donor aryl group and biorelevant imidazole-5-one as the acceptor (Scheme 25). 30 The scope of the protocol was investigated with a broad range of spirocyclopropanes and aldehydes to furnish the spirocyclic heterocycles. The reaction rate and diastereoselectivity of the final outcome could be greatly affected by the electronic properties and substitution patterns of the functional groups in the course of the reaction.…”

Computational insight into the mechanism and stereoselectivity of cycloaddition between donor–acceptor spirocyclopropane and aldehyde catalyzed by Brønsted acid TsOH

“…This step depended on the stability of the oxocarbenium ion formed in step 1. 21 However, due to the lack of studies on the ring-opening/cyclization of D-A cyclopropane and aldehyde catalyzed by a Brønsted acid to synthesize five-membered ring systems, the Fig. 1 Representative natural chiral tetrahydrofuran-type lignans.…”

“…Scheme 1 Ring-opening/cyclization reaction of D-A cyclopropane 1a with 3,4,5-trimethoxybenzaldehyde 2a to form diastereoisomers 3aa and 3' aa. 21 Organic & Biomolecular Chemistry Paper understanding of its mechanism is very limited, and there are no specific data to verify the hypothetical mechanism of the title reaction proposed by the researchers. From Scheme 2 it can be seen that the first intermediate cannot be formed directly from compound 1 in one step, which indicated that the mechanism reported by the authors was flawed and the details of the first step in Scheme 2 are not clear.…”

GaCl3-Mediated Cascade [2 + 4]-Cycloaddition/[4 + 2]-Annulation of Donor–Acceptor Cyclopropanes with Conjugated Dienes: Strategy for the Construction of Benzobicyclo[3.3.1]nonane Skeleton

“…It is known that donor–acceptor cyclopropanes (DACs), and 2-arylcyclopropane-1,1-diesters ( 1 ) in particular, are convenient building blocks for the synthesis of hetero- and carbocycles due to their ability to open the three-membered ring in the presence of Lewis acids with the generation of 1,3-zwitterionic intermediates. − On the other hand, a broad group of processes were studied in our research groups that occur via 1,2-zwitterionic gallium complexes 2 . Of these, reactions with unsaturated compounds such as alkenes, acetylenes, and conjugated dienes are particularly interesting for the generation of various carbocycles.…”